The Multicenter AIDS Cohort Study (MACS), a comprehensive cohort study ongoing since 1984, has contributed to the understanding of the natural history of HIV infection and the impact of highly active antiretroviral therapies (HAART). Combining genetic, virologic, immunologic and psychosocial approaches and utilizing the repository of specimens and long-term characterization of the participants, the extension of the support of the MACS will allow further elucidation of the biology of and response to HIV infection in the absence and presence of therapies, and distinguishing the effects of age, HIV and HAART on clinical outcomes. The MACS is ideally positioned to address these issues because of long-term standardized follow-up of 6,972 men, an extensive specimen repository and an appropriate control group consisting of HIV uninfected men with similar lifestyle behaviors and demographics. Additional strengths include following over 653 men before and after infection and with known dates of infection, experienced investigators and a broad network of outstanding collaborators with expertise in all aspects of HIV disease. This application further seeks support for the extension of the Center for the Analysis and Management of the MACS Data (CAMACS) to provide epidemiologic and statistical leadership to the MACS research agenda. The multicenter collaborative aspect, the complexities of characterizing the balance between beneficial and adverse effects of therapies, the selective use of treatment and the challenges inherent in choosing efficient study designs appropriate to the research questions require an analytical center to integrate HIV science with expertise in epidemiology, statistics and data management for MACS to successfully address the scientific aims as stated in Part A of this application. The specific aims of CAM ACS are to provide leadership and quality-assured systems to: 1) coordinate the research initiatives (includes effective communication, study protocol and form revision, periodic presentation of statistical characterizations pertinent to the scientific agenda);2) manage the data to facilitate analyses (includes edit, documentation, storage, and dissemination);3) provide statistical and epidemiological expertise in the design, analysis and interpretation of studies and to develop statistical and epidemiologic methodology;and 4) promote and track the use of MACS data/specimens.